Stromal cell-derived factor 1 as a biomarker of heart failure and mortality risk.
Stromal cell-derived factor 1 as a biomarker of heart failure and mortality risk.
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DOI：
10.1161/atvbaha.114.303579
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Levy D
中科院分区：
文献类型：
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作者：
Subramanian S;Liu C;Aviv A;Ho JE;Courchesne P;Muntendam P;Larson MG;Cheng S;Wang TJ;Mehta NN;Levy D
CXCL 12编码基质细胞衍生因子1 α（SDF-1），其与CXCR 4编码的受体结合。CXCL 12基因座的变异与冠状动脉疾病（CAD）和内皮祖细胞（EPC）数量相关，而CXCR 4基因座的变异与白细胞端粒长度（LTL）相关，后者已被证明与CAD相关。因此，我们研究了血浆SDF-1水平与心血管疾病（CVD）相关结局、危险因素、LTL和EPCs的关系。SDF-1在3359名心脏病研究参与者中进行了测量。我们使用考克斯回归分析SDF-1与新发CVD、心肌梗死（MI）、心力衰竭（HF）和全因死亡率的关系;我们使用线性回归分析评估SDF-1与危险因素、LTL和CD 34+细胞表型的相关性。在多变量模型中，较高的SDF-1水平与年龄较大，HDL胆固醇水平较低和吸烟有关。较高的SDF-1水平与较低的CD 34+细胞频率相关（p=0.02），但与LTL无关。在随访期间（中位数9.3年），有263例新发CVD事件，160例MI，200例HF事件和385例死亡。校正临床风险因素后，SDF-1水平与HF（p=0.04）和全因死亡率（p=0.003）相关，但与CVD（p=0.39）或MI（p=0.10）无关。在调整HDL胆固醇后，SDF-1水平与MI的相关性减弱。在调整传统的CVD风险因素后，SDF-1与HF和全因死亡风险相关。需要进一步的研究来确定SDF-1水平的测量是否具有临床实用性。
CXCL12 encodes stromal cell-derived factor 1 alpha (SDF-1), which binds to the receptor encoded by CXCR4. Variation at the CXCL12 locus is associated with coronary artery disease (CAD) and endothelial progenitor cell (EPC) numbers, while variation at the CXCR4 locus is associated with leukocyte telomere length (LTL), which has been shown to be associated with CAD. We therefore examined the relations of plasma SDF-1 levels to cardiovascular disease (CVD)-related outcomes, risk factors, LTL, and EPCs. SDF-1 was measured in 3359 Framingham Heart Study participants. We used Cox regression to examine relations of SDF-1 to new-onset CVD, myocardial infarction (MI), heart failure (HF), and all-cause mortality; we used linear regression to evaluate associations of SDF-1 with risk factors, LTL, and CD34+ cell phenotypes. In multivariable models, higher SDF-1 levels were associated with older age, lower levels of HDL cholesterol, and cigarette smoking. Higher SDF-1 levels were associated with lower CD34+ cell frequency (p=0.02), but not with LTL. During follow-up (median 9.3 years), there were 263 new-onset CVD events, 160 MIs, 200 HF events, and 385 deaths. After adjusting for clinical risk factors, SDF-1 levels were associated with HF (p=0.04) and all-cause mortality (p=0.003), but not with CVD (p=0.39) or MI (p=0.10). The association of SDF-1 levels with MI was attenuated after adjustment for HDL cholesterol. After adjusting for traditional CVD risk factors, SDF-1 is associated with HF and all-cause mortality risk. Further studies are needed to determine whether measurement of SDF-1 levels has clinical utility.